Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives

Abstract

Background: Alternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD).

Methods: Our review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next-generation sequencing (NGS) for AS events in IBD have been also discussed.

Results: Available evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis-associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro-fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third-generation sequencing (TGS), single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), will be desired with great expectations.

Conclusions: To our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.

Keywords: alternative splicing; basic mechanisms; biotechnological progresses; inflammatory bowel disease; perspectives.